This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To gain further insight on the diversity of host-pathogen interactions and how they contribute to pathogenesis of primate lentivirus infection, we examined the sequelae of intrarectal infection with a CCR5-tropic clade C SHIV1157ipd3N4 in pigtailed macaques. We reported last year for the first time a rapid and substantial loss of CD4+ T cells at multiple mucosal sites in pigtailed macaques following SHIV infection. By 2-3 wks post-infection, profound depletion of CD4+CCR5+ T cells cells and CD28-CD95+ effector memory cells were observed, consistent with the R5-tropism of SHIV1157ipd3N4. Two of the three animals that were studied beyond the acute phase of infection showed persistent plasma viremia for 48 wks, while the remaining one controlled its plasma viral load at baseline (102 copies/ml). Cross-clade neutralizing antibodies developed in both persistently viremic animals starting at 24 weeks after infection. However, both animals developed clinical signs consistent with simian AIDS and were euthanized. We are currently studying the evolution of viral sequences in these animals to gain a better insight on changes in the viral genome that may confer greater fitness for persistent infection in pig-tailed macaques.